1. Field of the Invention
The present invention relates to methods and compositions for treating cardiovascular disease and damaged cardiac tissue.
2. Description of the Related Art
Coronary artery disease (CAD) is the most common type of heart disease. CAD occurs when the coronary arteries become narrow as a result of atherosclerosis (Hansson G K. N Engl J Med. 2005; 352:1685-95). In CAD, the blood flow that supplies the heart muscle is decreased, which further leads to myocardial infarction (MI) and scar formation (Strauer B E, et al. Circulation. 2002; 106:1913-8). Unfortunately, the standard treatments including early revascularization using coronary intervention followed with supported pharmaceutical administration (Malik F I, et al. Science. 2011; 331:1439-43) are not sufficient. Eventually, accumulated cardiomyocyte loss contributes to heart failure. The American Heart Association has estimated that there are about 6 million patients with heart failure in the United States each year (Go A S, et al. Circulation. 2013; 127:e5-e245). Therefore, the ultimate goal of CAD treatment is to reduce cardiomyocytes death and to prevent further occurrence of heart failure (Rafii S, et al. Nat. Med. 2003; 9:702-12).
Previous studies have shown that cell therapy is a promising approach for heart repair post-MI (Murry C E, et al. Circulation. 2005; 112:3174-83; and Passier R, et al. Nature. 2008; 453:322-9). Some clinical trials have also demonstrated that autologous stem cell therapy can improve cardiac function after MI. These stem cells can participate in angiogenesis and provide paracrine factors to protect cardiomyocytes from the damage of ischemia. However, the results of these clinical studies remain controversial (Segers V F, et al. Nature. 2008; 451:937-42). The major reason may be that only a small portion of cells can survive and remain in the ischemia region after transplantation (Seeger F H, et al. Nat Clin Pract Cardiovasc Med. 2007; 4 Suppl 1:S110-3). For example, some studies have revealed that more than 90% of cells are lost during intra-myocardial injection due to contraction of the heart while the few resident cells have difficulty surviving in the highly hypoxic condition of the ischemic region (Segers 2008; and Laflamme M A, et al. Nat. Biotechnol. 2005; 23:845-56).
Therefore, a need still exists for cell therapy treatments for repairing damaged cardiac tissues.